SENSITIZATION TO THE CONDITIONED REWARDING EFFECTS OF MORPHINE - PHARMACOLOGY AND TEMPORAL CHARACTERISTICS

An unbiased place preference conditioning procedure was used to determ ine whether the repeated administration of morphine results in sensiti zation to its conditioned rewarding effects. Rats received once daily injections of saline or morphine (5.0 mg/kg; i.p.) for 5 days in a roo m distinct from that where conditioning would occur. Place preference conditioning commenced 72 h later. A minimum of three drug conditionin g sessions was necessary for the establishment of morphine-induced con ditioned place preferences in saline-pretreated rats. The minimum dose producing this effect was 5.0 mg/kg. in animals pre-exposed to morphi ne, significant place preferences occurred after only two drug conditi oning sessions and in response to doses of 3.0 mg/kg and greater. The augmented response to morphine was apparent when conditioning commence d 3, 10 or 21 days after the cessation of morphine pretreatment. It wa s not apparent when conditioning commenced 1 day after treatment cessa tion. An enhanced response to morphine was also observed in rats which had previously received either fentanyl(0.016 mg/kg/day) or nicotine (0.4 mg/kg/day) for 5 days. Animals which received morphine or fentany l in combination with naloxone (0.5 mg/kg; s.c.) for 5 days failed to exhibit a conditioned response to morphine. When, however, naloxone wa s administered in combination with nicotine, significant morphine-indu ced place preferences were still seen. These data demonstrate that bot h sensitization and cross-sensitization develop to the conditioned rew arding effects of morphine. Furthermore, they indicate that the sensit ization induced by morphine and fentanyl, but not nicotine, is opioid- receptor mediated.